Chronic inflammation mediated by Th2-type cytokines can lead to morbidity and mortality in allergy/asthma. Therefore, one of our major research goals has been to understand the immunological mechanisms controlling Th2 response development, and to design effective immunotherapies to treat or prevent such reactions. In particular, we are interested in understanding how chronic allergic disease leads to tissue remodeling and fibrosis. The development of fibrous tissue is part of the normal process of healing after injury. Nevertheless, in some circumstances, there is a destructive accumulation of excess collagen that interferes with the normal function of the affected tissue. Although there is a great deal of mechanistic information regarding the process of scar tissue formation, there are still large gaps in our understanding of the role of inflammatory cells and cytokines in intiating the fibrotic process. We are in the process of initiating a series of studies examining the role of Nitrous Oxide and Fibrosis in our mouse models of airway hyperresponsiveness. We are hoping that elucidating the mechanisms leading to tissue pathology and fibrosis may lead to more effective strategies for immunological intervention in this and a variety of other chronic diseases.